In April 2011, former Mexican President Vicente Fox sat before an audience at the University of Colorado at Boulder and in his baritone voice and frank tone urged Americans to legalize marijuana. His thrust: it could help enervate Mexico’s violent drug cartels. “The drug consumer in the U.S. yields billions of dollars, money that goes back to Mexico to bribe police and money that buys guns,” Fox said. “So when you question yourselves about what is going on in Mexico, it depends very much on what happens in this nation.”

At the time, many pundits warned that legalization was a nonstarter. But on Tuesday, voters in Colorado and Washington state did exactly what Fox called for: they approved landmark amendments to legalize, regulate and tax marijuana.

As supporters in Colorado jumped up and down, shouting “64, 64” after the amendment’s ballot number, the seismic implications of the reforms began to be slowly digested by activists across the globe, especially in drug-war-torn Mexico. “It was very emotional,” says Jorge Hernández, president of the Collective for an Integral Drug Policy, which is pushing for legalization in Mexico. “Now we are not like madmen in the desert. This transforms the debate.” That’s because the U.S. referendums signal the first time voters have approved the full legalization of marijuana anywhere on the planet, giving advocates from Mexico to Moscow bona fide cases to cite and follow. Even the famous cannabis coffee shops of Amsterdam exist only through an ambiguous policy of toleration often referred to as decriminalization, something Portugal has pursued as well. A 2009 Mexican law also decriminalized possession of small amounts of cannabis and other drugs, but production and selling has been left in the hands of bloodthirsty traffickers.

Reformists in Colorado and Washington State are still far from claiming an all-out victory. Marijuana remains illegal under U.S. federal law, setting up a confrontation between cannabis growers and the re-elected Obama Administration. Furthermore, U.N. treaties oblige all signatories to prohibit the legalization of marijuana as well as cocaine, heroin and methamphetamine.

Nevertheless, entire countries may soon follow Colorado’s example, forcing an international review of the issue. Uruguayan President José Mujica is pushing to legalize marijuana by the end of the year — legislation there would even make the government the drug’s sole legal seller — and there is strong support for reforms in Argentina and Brazil. “What happened on Tuesday was a game changer. It will have a huge political and symbolic impact,” says drug analyst Alejandro Hope from the Mexican Institute for Competitiveness think tank. “Now it would be very hard for the U.S. to tell people not to legalize marijuana.”

The institute released a report last week saying that the U.S. state amendments could dent Mexican traffickers’ finances as gringo consumers buy more locally produced grass than the Mexican product, which it said accounts for a third of the Mexican drug cartels’ revenue. American smokers currently import from 40% to 70% of their cannabis from Mexico, according to the report. Legalization in just two states, of course, may not have a very dramatic effect. What’s more, Mexican cartels traffic other narcotics, including cocaine, heroin and meth, and commit lucrative crimes from kidnapping to extortion, so even nationwide U.S. marijuana legalization would not destroy the cartels. Still, it could substantially weaken them.

Mexican President Felipe Calderón did not immediately comment on the votes in Colorado and Washington. Back in 2010, he had spoken against a similar initiative to legalize marijuana in California. However, after the huge cost of his military offensive against cartels, with about 60,000 drug-related murders since he took office in 2006, he has questioned prohibition in more recent statements — including a particularly frustrated speech last year after narcos massacred 52 innocent people in a Monterrey casino. In September, Calderón joined Latin American Presidents from Guatemala to Colombia in demanding a new U.N. debate on drug policy.

Calderón leaves office on Dec. 1, passing the torch to President-elect Enrique Peña Nieto, who has already said he wants to prioritize reducing murders above busting drugs. The new amendments in the U.S. will raise further questions about whether Mexico should send its soldiers and police to burn marijuana fields and seize the cartels’ vacuum-packed boxes of weed. “Why are we busting trucks of marijuana in Mexico when they are selling it over the counter in some U.S. states?” former Foreign Minister Jorge Castañeda asked on Mexican radio on Wednesday. “There is no logic to it. It is schizophrenic.”